BI 836858 Dose Escalation in Patients With Refractory or Relapsed Acute Myeloid Leukemia and in Patients in Complete Remission With High Risk to Relapse

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by Boehringer Ingelheim
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01690624
First received: September 13, 2012
Last updated: August 22, 2016
Last verified: August 2016
  Purpose
Patients with acute myeloid leukemia who experience a relapse after at least one prior regimen may be enrolled in this trial. In addition, acute myeloid leukemia patients who are in complete remission with high risk to relapse may be eligible for this trial. The trial will examine whether monotherapy with BI 836858 is safe and tolerable at escalating dose levels.

Condition Intervention Phase
Leukemia, Myeloid, Acute
Drug: BI 836858
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I, Open-label, Cohort Dose Escalation Trial With BI 836858 in Patients With Refractory or Relapsed Acute Myeloid Leukemia and Patients With Acute Myeloid Leukemia in Complete Remission With High Risk to Relapse.

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Determination of the maximum tolerated dose of BI 836858 [ Time Frame: up to 4 weeks ] [ Designated as safety issue: No ]
  • Number of patients with dose limiting toxicity during maximum tolerated dose evaluation for patients with refractory or relapsed acute myeloid leukemia [ Time Frame: up to 4 weeks ] [ Designated as safety issue: No ]
  • Number of patients with dose limiting toxicity during maximum tolerated dose evaluation for acute myeloid leukemia patients in complete remission with high risk to relapse [ Time Frame: up to 4 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Maximum measured plasma concentration (Cmax) [ Time Frame: up to 168 hours ] [ Designated as safety issue: No ]
  • Time from dosing to the maximum plasma concentration (tmax) [ Time Frame: up to 168 hours ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve over the time interval of one week (AUC0-168) [ Time Frame: up to 168 hours ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve over the time interval of one treatment cycle (AUC0-tz) [ Time Frame: up to 336 hours ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve over the time interval from zero extrapolated to infinity (AUC0-infinity) [ Time Frame: up to 168 hours ] [ Designated as safety issue: No ]
  • Terminal half-life (t1/2) [ Time Frame: up to 168 hours ] [ Designated as safety issue: No ]
  • Mean residence time after intravenous infusion (MRT) [ Time Frame: up to 168 hours ] [ Designated as safety issue: No ]
  • Total plasma clearance (CL) [ Time Frame: up to 168 hours ] [ Designated as safety issue: No ]
  • Apparent volume of distribution during the terminal phase (Vz) [ Time Frame: up to 168 hours ] [ Designated as safety issue: No ]
  • Volume of distribution after intravenous infusion at steady state (Vss) [ Time Frame: up to 168 hours ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve over the time interval from zero to the time of the last quantifiable data point (AUC0-tz) [ Time Frame: up to 168 hours ] [ Designated as safety issue: No ]
  • Best overall response rate according to International Working Group (IWG) criteria (for refractory or relapsed acute myeloid leukemia patients only) [ Time Frame: up to 22 months ] [ Designated as safety issue: No ]
  • Progression free survival for patients with refractory or relapsed acute myeloid leukemia [ Time Frame: up to 22 months ] [ Designated as safety issue: No ]
  • Time to treatment failure for patients with refractory or relapsed acute myeloid leukemia [ Time Frame: up to 22 months ] [ Designated as safety issue: No ]
  • Time to treatment failure for acute myeloid leukemia patients in complete remission with high risk to relapse [ Time Frame: up to 22 months ] [ Designated as safety issue: No ]
  • Progression free survival for acute myeloid leukemia patients in complete remission with high risk to relapse [ Time Frame: up to 22 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 36
Study Start Date: September 2012
Estimated Study Completion Date: March 2019
Estimated Primary Completion Date: March 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Patients with relapsed or refractoryAML
Patients with acute myeloid leukemia who have relapsed after 1 prior treatment.
Drug: BI 836858
Monotherapy with BI 836858 administered as intravenous infusion

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Diagnosis of relapsed or refractory AML with at least one prior treatment for acute myeloid leukemia and patients with diagnosis of acute myeloid leukemia in complete remission with high risk to relapse.
  2. Expression of CD33 on more than 30% of bone marrow blasts at screening for patients with refractory or relapsed acute myeloid leukemia is required. CD33 positive expression of bone marrow blasts at the time of initial acute myeloid leukemia diagnosis is sufficient for those patients in complete remission with high risk to relapse.
  3. Eastern Cooperative Oncology Group Performance Status 0, 1 or 2
  4. Age 18 years or older
  5. Written informed consent which is consistent with International Conference on Harmonization, Good Clinical Practice (ICH-GCP) guidelines and local legislation.

Exclusion criteria:

  1. Patients with acute promyelocytic leukemia according to WHO definition.
  2. Patients with refractory or relapsed acute myeloid leukemia > 5.000 blasts in the peripheral blood.
  3. Anti-leukemia therapy within two weeks before first treatment with BI 836858, 4 weeks for biologics. Parallel treatment with Hydroxyurea ia allowed with refractory or relapsed acute myeloid leukemia patients.
  4. Allogeneic stem cell transplantation within the last 28 days before first treatment with graft versus host disease requiring more than 20 mg of steroids per day. Steroid dosage must be stable within two weeks prior to start of treatment.
  5. Patients who are candidates for allogeneic stem cell transplantation (for patients with refractory or relapsed acute myeloid leukemia).
  6. Second malignancy currently requiring active therapy.
  7. Symptomatic central nervous system involvement
  8. Aspartate amino transferase (AST) or alanine amino transferase (ALT) greater than 2.5 times the upper limit of normal (ULN), or AST or ALT greater than 5 times the ULN for those with Gilbert syndrome.
  9. Prothrombin time (PT) >1.5 x ULN for subjects not on therapeutic vitamin K antagonists (phenprocoumon, warfarin)
  10. Bilirubin greater than 1.5 mg/dl (>26 µmol/L) unless elevation is thought to be due to hepatic infiltration by AML, Gilbert syndrome, or hemolysis.
  11. Serum creatinine greater than 2.0 mg/dl
  12. Known human immunodeficiency virus (HIV) infection or active hepatitis B virus or hepatitis C virus infection.
  13. Concomitant intercurrent illness, or any condition which in the opinion of the Investigator, would compromise safe participation in the study, e.g. active severe infection, unstable angina pectoris, new onset of exacerbation of a cardiac arrhythmia
  14. Psychiatric illness or social situation that would limit compliance with trial requirements
  15. Concomitant therapy, which is considered relevant for the evaluation of the efficacy or safety of the trial drug
  16. Female patients of childbearing potential who are sexually active and unwilling to use a medically acceptable method of contraception during the trial and for 6 months after the last administration of BI 836858
  17. Male patients with partners of childbearing potential who are unwilling to use condoms in combination with a second effective method of contraception during the trial and for 6 months after the last administration of BI 836858
  18. Pregnant or nursing female patients
  19. Treatment with another investigational agent under the following conditions:

    1. Within two weeks (4 weeks for biologics or 5 half-lives, whichever is longer) of first administration of BI 836858; or
    2. Patient has persistent toxicities from prior anti-leukemic therapies which are determined to be relevant by the Investigator.
    3. Concomitant treatment with another investigational agent while participating in this trial.
  20. Prior treatment with a CD33 antibody
  21. Patient unable or unwilling to comply with the protocol.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01690624

Contacts
Contact: Boehringer Ingelheim Call Center 1-800-243-0127 clintriage.rdg@boehringer-ingelheim.com

Locations
United States, Illinois
1315.1.1003 Boehringer Ingelheim Investigational Site Recruiting
Chicago, Illinois, United States
United States, Maryland
1315.1.1006 Boehringer Ingelheim Investigational Site Recruiting
Baltimore, Maryland, United States
United States, Missouri
1315.1.1004 Boehringer Ingelheim Investigational Site Completed
St. Louis, Missouri, United States
United States, New York
1315.1.1002 Boehringer Ingelheim Investigational Site Completed
New York, New York, United States
United States, Ohio
1315.1.1001 Boehringer Ingelheim Investigational Site Recruiting
Columbus, Ohio, United States
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01690624     History of Changes
Other Study ID Numbers: 1315.1 
Study First Received: September 13, 2012
Last Updated: August 22, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on August 25, 2016